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J Atzpodien

Publications and source records attributed to J Atzpodien.

At least 109 records · Page 6Linked to original sources
PubMed1992

Analysis of the 14;18 translocation in cutaneous lymphomas using the polymerase chain reaction.

A series of 25 cutaneous B-cell lymphoid proliferations was analyzed for the presence of the (14; 18) translocation using the polymerase chain reaction. Junctional sequences of rearranged chromosomes 14 and 18 were amplified in vitro, and t (14; 18) specific sequences were detected in 1 of 14 primary cutaneous B-cell lymphomas, in 3 of 8 primary nodal B-cell lymphomas and in none of 3 B-cell pseudolymphomas. These results indicate that the t (14; 18) may occur in a small subset of primary cutaneous lymphoma. However, the difference in incidence of the t (14; 18) between primary nodal and primary cutaneous lymphomas suggests that different molecular mechanisms are involved in the pathogenesis of these lymphomas.

Base Sequence↗
PubMed1992

Pretreatment natural killer antigen density correlates to clinical response in tumor patients receiving long-term subcutaneous recombinant interleukin-2 and recombinant interferon-alpha.

We evaluated density of the natural killer (NK) cell-associated CD56 antigen on circulating NK cells of 47 patients with advanced renal cell carcinoma. Patients received a combination of low-dose subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as home therapy. Antigen density of CD56 before therapy was 2.2-fold higher (P < 0.005) in patients who subsequently achieved a complete or partial remission when compared with patients who presented with progressive disease on therapy. After a 6-week treatment cycle, NK cells of treatment responders expressed significantly (2.1-fold; P < 0.005) more CD56 antigens than NK cells in nonresponding patients. These results suggested a potential role of both pre- and posttreatment NK antigen density levels as a biologic correlate to treatment response.

Antigens, CD↗
PubMed1992

Biologic and therapeutic efficacy of mafosfamide in patients with metastatic renal cell carcinoma.

It is well known that oxazaphosphorines [e.g., cyclophosphamide and 4-hydroperoxycyclophosphamide (mafosfamide)] are potent immunosuppressive agents. Under the proper conditions, they can potentiate immune responses as well. Immunomodulation represents a major breakthrough in the management of chemotherapy-resistant tumors. Thus, we evaluated the clinical and laboratory sequelae of low to intermediate doses (100-1000 mg/m2) of mafosfamide administered to 16 patients. Four weeks after therapy, one patient had a complete remission, eight patients presented with stable disease, and seven patients did not respond. Clinical and laboratory toxicity was mild and totally reversible, and therapy was well tolerated in all patients. Analyses of phenotypic cell surface antigens on circulating peripheral blood mononuclear cells showed inconsistent alterations of the CD4/CD8 ratio, initial depletion with later rebound of CD8+ cells, increase of CD20+ cells, and a mafosfamide dose-dependent regulation of natural killer-like cells as characterized by CD16 and CD56 positivity. Cell-mediated cytotoxicity against K562 target cells peaked 1 day after therapy and was most pronounced in patients who had received 300 mg/m2 mafosfamide, whereas cytotoxicity against Daudi targets was essentially unchanged, consistent with an increase in natural killing activity without augmentation of lymphokine activated killing. We conclude that mafosfamide administration at low to intermediate doses can be performed with good safety and tolerance; immunophenotypic analyses and cytotoxicity assays showed most pronounced alterations in patients receiving low doses of mafosfamide. These observations support the use of mafosfamide in the attempt to augment antitumor immune responses.

Adjuvants, Immunologic↗
PubMed1992

Autologous bone marrow transplantation for acute myelogenous leukemia using 4-hydroperoxycyclophosphamide and VP-16 purged bone marrow.

Thirty adult patients with acute myelogenous leukemia (AML) in remission were treated with hyperfractionated total body irradiation, VP-16, and cyclophosphamide followed by infusion of autologous bone marrow purged with 4-hydroperoxycyclophosphamide and VP-16. Fifteen patients were transplanted in first remission (R1), 13 in second remission (R2), and two in third remission (R3). All patients had hematopoietic engraftment. The median time to achieve a white blood cell count of 1.0 x 10(9)/l and a neutrophil count of 500 x 10(6)/l was 32 days. The median time to achieve an unsupported platelet count of 50 x 10(9)/l was 70 days. There were four transplant-related deaths, all in patients in R2. Ten patients have relapsed, including both patients transplanted in R3. The disease-free survival (DFS) of all patients is 52%, median follow-up not yet reached. Although the number of patients in each group is small and follow-up is limited, there is a trend toward improved actuarial DFS in patients transplanted in R1 compared with patients transplanted in R2 (72 vs 39%; p = 0.081). Use of VP-16 in the conditioning regimen as well as in the purging procedure is feasible in the treatment of patients with AML.

Adult↗
PubMed1991

Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes.

Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor-alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.

Carcinoma, Renal Cell↗
PubMed1991

The out-patient use of recombinant human interleukin-2 and interferon alfa-2b in advanced malignancies.

We studied the safety, tolerance, and clinical effects of the combined administration of subcutaneous recombinant human interleukin-2 and interferon alfa-2b in 54 patients with advanced cancer, for whom no effective standard therapy was available. Treatment courses consisted of a 2-day interleukin-2 pulse (14.4-18 million units (MU) m2/day), followed by 3.6 up to 4.8 MU/m2/day, 5 days per week, over 6 consecutive weeks and interferon alfa-2b at 3 up to 6 MU/m2, administered two-three times weekly for 6 weeks. Overall, patients received more than 90% of the projected dose of interleukin-2 and interferon alfa-2b, respectively. Of 54 evaluable patients (32 renal cell cancer, 12 melanoma, eight colorectal cancer, one B-cell lymphoma, one Hodgkin's disease), four complete responses occurred in patients with renal cell carcinoma, and a greater than 50% reduction in tumour size (partial response) in six renal cell carcinoma patients and one melanoma patient. Moreover, 21 patients (13 renal carcinoma) had stable disease. The median duration of response was 19 months (range 16-22 months) in complete responders. Clinical responses were associated with a mean peripheral blood eosinophil count of more than 1,000/microL (P less than 0.05 versus non-responders). Systemic toxicities included fever, chills, nausea, anorexia, and hypotension limited to WHO grades I and II in more than 80% of patients treated. No treatment-related deaths occurred. This combination of subcutaneously administered recombinant interleukin-2 and interferon alfa-2b has significantly diminished the side effects normally observed with high-dose intravenous recombinant interleukin-2, which requires admission to hospital. It has been shown to induce objective tumour regression in out-patients with progressive metastatic renal cell carcinoma and malignant melanoma.

Adult↗
PubMed1991

Diminished expression of interleukin-2 receptors in vivo after prior chemotherapy in advanced cancer patients receiving recombinant interleukin-2.

In a phase I/II dose escalation study performed at our institution, a total of 14 advanced metastatic cancer patients received between 4 and 16 weeks of subcutaneous recombinant interleukin-2. Doses were escalated at weekly intervals, starting at 1.8 million IU/m2/day up to a maximum dose of 14.4 million U/m2 daily. When comparing patients with (n = 4) and without (n = 7) prior chemotherapy on day 0 (i.e., before rIL-2), both patient groups exhibited Tac IL-2 receptor (CD25) positive peripheral blood lymphocytes at equal levels of positivity (8%). In contrast, 4-week systemic treatment with subcutaneous rIL-2 at escalating dose levels revealed a significant difference in the up-regulation by interleukin-2 of CD25 cell surface receptor. Thus, after 4 consecutive weeks of treatment, patients without previous chemotherapy showed a mean CD25 positivity of peripheral blood lymphocytes at 38%, as compared with 22% in patients who did receive prior chemotherapy (p less than 0.05). These data suggest that chemotherapy pretreatment may have a significant effect on biological response to rIL-2 in vivo.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

alpha-Interferon and interleukin-2 in renal cell carcinoma: studies in nonhospitalized patients.

We have studied the safety, tolerance, and clinical effects of the combined administration of subcutaneous recombinant human interleukin-2 and alpha-interferon in 34 patients with metastatic renal cell carcinoma who had undergone tumor nephrectomy. Treatment courses consisted of a 2-day interleukin-2 pulse (14.4 to 18.0 million IU/m2/d), followed by 3.6 to 4.8 million IU/m2/d, 5 days per week, over 6 consecutive weeks, and alpha-interferon at 3.0 to 6.0 million U/m2, administered 2 to 3 times weekly for 6 weeks. Patients received more than 90% of the projected dose of interleukin-2 and alpha-interferon, respectively. Of 34 patients with metastatic progressive renal cell carcinoma in this study, four had complete response and six had greater than 50% reduction in tumor size (ie, partial response). There were, in addition, 13 patients with stable disease. So far, all complete responses have been durable, with a median duration of 23+ months. Clinical responses were associated with a mean peripheral blood eosinophil count of more than 1,000/microliters (P less than .05). The predominant toxicities included fever, chills, nausea, anorexia, and hypotension, and were limited to World Health Organization grades 1 and 2 in more than 80% of patients treated. No treatment-related deaths occurred. This combination of subcutaneously administered recombinant interleukin-2 and alpha-interferon has significantly reduced the side effects normally observed with high-dose intravenous recombinant interleukin-2. It can induce objective tumor regressions in patients with progressive metastatic renal cell carcinoma. Unlike the intravenous schedules developed by Rosenberg and West, which require admission to hospital, all the patients in this study were treated in an outpatient setting.

Adult↗
PubMed1990

Establishment and characterization of a granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line.

A new human myeloid cell line has been established recently from the bone marrow cells of a patient with chronic myelogenous leukemia in blast crisis. The active proliferation and survival of the cells in RPMI 1640 medium containing fetal calf serum are clearly dependent on the presence of either natural or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Despite permanent culturing in rhGM-CSF (100 U/mL), the cells do not differentiate and bear the myelomonocytic surface markers CD34, CD13, CD36, as well as HLA-DR, but not CD3, CD7, CD10, CD11b, CD14, CD20, or CD42b. The predominant karyotype, apart from tetraploidy in several cells, is 45, XX, -9, -17, -19, -22, 7p-, 9q+ (der t[9;22]), der (13q), with three additional marker chromosomes, from which one was observed in the patient's leukemic cells. On BglII-digested DNA, Southern blot analysis with bcr 5' as the probe detected two additional hybridizing restriction fragments of 8.6 and 11.0 kilobase pairs.

Blast Crisis↗
PubMed1990

Home therapy with recombinant interleukin-2 and interferon-alpha 2b in advanced human malignancies.

The safety, tolerance, and clinical effects of a home therapy regimen of recombinant human interleukin-2 (rIL-2) and interferon-alpha 2b (IFN-alpha 2b) self injected subcutaneously have been assessed in 35 patients with advanced cancer refractory to standard therapy. 52 treatment cycles were given, each consisting of a 2-day rIL-2 pulse of 9.0 million IU/m2 every 12 h, followed by 6 weeks of rIL-2 1.8 million IU/m2 twice daily for 5 days per week and of IFN-alpha 2b 5.0 million U/m2 thrice a week. The main adverse effects were fever, chills, nausea, anorexia, and hypotension and were limited to WHO grades of severity I and II in 29 of 35 patients. No treatment-related deaths occurred. The response rates among patients with renal-cell carcinoma were similar to those reported for high-dose intravenous regimens of interleukin-2 that are toxic and have to be given in hospital.

Adult↗
PubMed1990

Cancer, cytokines, and cytotoxic cells: interleukin-2 in the immunotherapy of human neoplasms.

Modern immunotherapy of human cancer has evolved as a rapidly expanding field of clinical and experimental research. Employing the systemic application of recombinant interleukin-2 (IL-2) in humans, Rosenberg and colleagues from the National Cancer Institute reported the regression of advanced metastatic tumors in approximately 10%-30% of patients treated. The additional adoptive transfer of autologous patient-derived activated lymphocytes was performed to enhance therapeutic efficacy. While the exact mechanisms of IL-2 based immunotherapy in cancer remain unclear, it has been hypothesized that both the IL-2 activated lymphocyte and its secretory products such as interferon-gamma or tumor-necrosis factor beta may contribute to the lysis of tumor cells in vivo. Accordingly, research has been directed toward enhancing both the activation state and the specificity of IL-2 induced killer cells in humans. Based on in vitro and animal data, the retransfusion of tumor-infiltrating lymphocytes has been shown to mediate the regression of metastatic neoplasms in up to 50% of patients receiving systemic IL-2. Considerable toxicity from the use of high-dose IL-2 has prompted attempts to develop low-dose regimens which allow for the outpatient treatment of patients presenting poor prognosis. While in most clinical trials involving IL-2, patient follow-up has been short, and no or only limited data have become available from controlled prospective and randomized clinical studies, IL-2 has shown some promise in patients with metastatic renal cell cancer or malignant melanoma. Novel approaches toward the improvement of clinical efficacy of IL-2 include local (e.g., intracavitary) application or combinations with other cytokines such as interferon-alpha or cytostatic drugs.

Biological Factors↗
PubMed1990

Treatment of metastatic renal cell cancer patients with recombinant subcutaneous human interleukin-2 and interferon-alpha.

We treated 17 patients who had progressive metastatic renal carcinoma with a combination of subcutaneous recombinant human interleukin-2 (administered every 12 hours, at 9.0 million IU/m2 on days one and two, followed by 1.8 million IU/m2, five days per week, over six consecutive weeks) and interferon-alpha 2b (given at 5 million U/m2 three times weekly, for six consecutive weeks). Treatment courses were repeated in patients presenting with stable or regressive disease after the six weeks of combination therapy (11 of 14 evaluable). Two and three of 14 evaluable patients achieved complete and partial remissions, respectively. Toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (WHO) fevers, chills, malaise, nausea/vomiting, and anorexia in more than two-thirds of the patients treated.

Carcinoma, Renal Cell↗
PubMed1990

Immunophenotypic analysis of lymphocytes and myeloma cells in patients with multiple myeloma.

The immunological phenotypes of lymphocytes and myeloma cells in 48 patients with multiple myeloma (MM) were analyzed using a panel of monoclonal antibodies (mAbs). Myeloma cells were positive for OKT10, BL3, PCA1 and BA2. In a few cases, they were also positive for the B cell-associated antigens J5, B1 and I2. Eight of 48 cases had more than 15% J5-positive lymphocytes, and some lymphocytes in MM expressed plasma cell-associated antigens (PCA1, BL3, OKT10), suggesting a possible clonal involvement. These observations demonstrate the heterogeneity of surface antigen expression of myeloma cells and suggest that BL3, PCA1, BA2 and J5 may be useful mAbs for purging myeloma cells from bone marrow for autologous transplantation.

Antibodies, Monoclonal↗
PubMed1990

Photoradiation methods for purging autologous bone marrow grafts.

The potential of various photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants is discussed in this paper. The results with fluorescent dyes, Dihematoporphyrin Ether (DHE) and Merocyanine-540 (MC-540) are detailed. Following photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity towards lymphoid and myeloid neoplastic cells, but had significantly less effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, cALLa positive acute lymphoblastic leukemia (Reh), and diffuse histiocytic B-cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 ug/ml and MC-540 concentrations of 15 to 20 ug/ml, clonogenic tumor cells could be reduced by more than 4 logs, when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells, and on normal marrow myeloid (CFU-GM) precursors, when the drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15-20 ug/ml) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). Using DHE (2.5 ug/ml), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared, following sequential drug and light exposure of cells, while simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. The data from various centers is briefly discussed with special emphasis on clinical trials. Our results provide a useful model for leukemia and lymphoma cells and suggest that these phototherapy experiments can be implemented into clinical trials.

Bone Marrow↗
PubMed1990

A highly sensitive quantitative bioassay for human granulocyte-macrophage colony-stimulating factor.

Based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) dependency of a newly established human myeloid cell line GM/SO, we developed a highly specific and sensitive bioassay for human GM-CSF. The presence of bioactive GM-CSF could be determined by measuring the formazan concentration produced from MTT by the cells that survived and proliferated in the presence of either natural or recombinant human GM-CSF. With this assay we were able to quantify the level of GM-CSF in two human sera as well as in conditioned media from human bladder cell carcinoma cell line 5637, a human fibroblast line, and phytohemagglutinin-stimulated peripheral blood mononuclear cells. The sensitivity of the assay allows measurement of concentrations of GM-CSF as low as 0.1 U/ml.

Biological Assay↗
PubMed1990

Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study.

Recombinant interleukin-2 (rIL-2; EuroCetus, Amsterdam, Netherlands) was studied in an outpatient phase II trial in 14 patients with progressive metastatic renal carcinoma, malignant melanoma, and colorectal cancer. Escalating doses of rIL-2 were administered as subcutaneous bolus every 12 hours, starting at 0.3 million U/m2/d. A 100% dose increase occurred at weekly intervals, up to a maximum of 2.4 million U/m2/d. Responding patients or patients with stable disease after 4 weeks of rIL-2 (n = 9) were continued on maintenance therapy at 1.8 million U/m2 of rIL-2 administered once weekly. After 12 weeks of therapy, one renal cell cancer patient had a partial regression in lung metastases. Bolus injection of rIL-2 (1.2 million U/m2) resulted in peak serum levels of 25 to 30 U/ml. Toxicity of this regimen was moderate, with local inflammation at the injection sites, grade I-II (World Health Organization) malaise, nausea and/or vomiting, and fevers in 70% to 100% of patients treated. Thyroid dysfunction was observed in 10 patients receiving subcutaneous rIL-2; four of these patients had laboratory evidence of hyperthyroidism, and one had hypothyroidism. rIL-2-induced toxicity reversed spontaneously after cessation of treatment. In all patients receiving rIL-2, a dose-dependent increase in peripheral blood lymphocyte and eosinophil counts was noted, with a mean of 2.6 and 3.8 x 1,000/microliters after 4 weeks of therapy; mean lymphocyte and eosinophil counts were measured at 2.0 and 2.4 x 1,000/microliters in patients who received prior high-dose chemotherapy, compared with 3.2 and 5.1 x 1,000/microliters in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Anorexia↗
PubMed1989

Ex vivo treatment of myeloma cells by 4-HC, VP-16, LAK cells and antibodies.

To assess the usefulness of 4-hydroperoxycyclophosphamide (4-HC) and Etoposide (VP-16) as a purging agent for myeloma cells in bone marrow ex-vivo, myeloma cell lines (SK-RCS-1, RPMI-8226), lymphoma cell line (SK-DHL-2) and normal bone marrow (BM) cells were treated at different concentrations of 4-HC, VP-16. In separate experiments, LAK cells or antibodies were also used to treat the above cell lines. Clonogenic tumor cells from all three cell lines could be reduced by more than 4 logs, when treated alone or as a mixture with irradiated normal bone marrow cells at a 4-HC concentration of 60 mumol/l. Under similar conditions, approximately 1% of normal BM myeloid progenitor granulocyte-macrophage colony forming cells (CFU-GM) survived. The results with LAK cells and antibodies were also encouraging. These observations support the use of various purging methods for myeloma cells for autologous bone marrow transplantation.

Antibodies, Monoclonal↗